Stimulation of β2-adrenergic receptor increases CFTR function and decreases ATP levels in murine hematopoietic stem/progenitor cells

Teresa Trotta, Lorenzo Guerra, Donatella Piro, Maria d'Apolito, Claudia Piccoli, Chiara Porro, Ida Giardino, Silvia Lepore, Stefano Castellani, Sante Di Gioia, Antonio Petrella, Angela Bruna Maffione, Valeria Casavola, Nazzareno Capitanio, Massimo Conese

Research output: Contribution to journalArticle

Abstract

Background: The chloride channel CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is expressed by many cell types, including hematopoietic stem/progenitor cells (HSPCs). In this study, we sought to better comprehend the regulation of CFTR activity in HSPCs, namely by beta-adrenergic stimuli. Methods: The expression of β2-adrenergic receptor (β2-AR) in murine Sca-1+ HSPCs was investigated by immunofluorescence/confocal microscopy and flow-cytometric analysis. Association with CFTR was assessed by immunoprecipitation. HSPCs were evaluated for ATP content and CFTR activity by means of luminometric and spectrofluorometric methods, respectively, upon stimulation with salbutamol. Results: HSPCs express β2-AR over the whole plasma membrane and are associated in cellula with both the immature and mature forms of CFTR. β2-AR was predominantly expressed by HSPCs with bigger size. CFTR channel activity was increased by salbutamol treatment and this activation was inhibited by either a specific CFTR inhibitor (CFTRinh172) or a β2-AR receptor inhibitor (ICI 118,551). Intracellular ATP levels were reduced by salbutamol stimulation and this effect was reversed when ICI 118,551 or CFTR inhibitors were present. A trend in the increase of extracellular ATP upon salbutamol stimulation was observed. Conclusions: In HSPCs, CFTR is regulated by β2-adrenergic receptor stimulation determining intracellular ATP depletion.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalJournal of Cystic Fibrosis
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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Keywords

  • Adrenergic receptor
  • ATP
  • CFTR
  • Hematopoietic stem/progenitor cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Trotta, T., Guerra, L., Piro, D., d'Apolito, M., Piccoli, C., Porro, C., Giardino, I., Lepore, S., Castellani, S., Di Gioia, S., Petrella, A., Maffione, A. B., Casavola, V., Capitanio, N., & Conese, M. (2015). Stimulation of β2-adrenergic receptor increases CFTR function and decreases ATP levels in murine hematopoietic stem/progenitor cells. Journal of Cystic Fibrosis, 14(1), 26-33. https://doi.org/10.1016/j.jcf.2014.08.005